Trial Outcomes & Findings for A Study of Tirzepatide (LY3298176) Versus Insulin Degludec in Participants With Type 2 Diabetes (NCT NCT03882970)

Last Updated: 2022-01-19

Results Overview

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates Baseline + Pooled Country + Baseline Oral Antihyperglycemic Medication (OAM) Use (Metformin (Met), Met plus SGLT-2i) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1444 participants

Primary outcome timeframe

Baseline, Week 52

Results posted on

2022-01-19

Participant Flow

Participant milestones

Participant milestones
Measure	5 mg Tirzepatide 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.	10 mg Tirzepatide 10 mg tirzepatide administered SC once a week.	15 mg Tirzepatide 15 mg tirzepatide administered SC once a week SC.	Insulin Degludec Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.
Overall Study STARTED	359	361	359	365
Overall Study Received at Least One Dose of Study Drug	358	360	359	360
Overall Study COMPLETED	333	321	340	331
Overall Study NOT COMPLETED	26	40	19	34

Reasons for withdrawal

Reasons for withdrawal
Measure	5 mg Tirzepatide 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.	10 mg Tirzepatide 10 mg tirzepatide administered SC once a week.	15 mg Tirzepatide 15 mg tirzepatide administered SC once a week SC.	Insulin Degludec Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.
Overall Study Adverse Event	5	7	3	1
Overall Study Death	1	2	1	1
Overall Study Lost to Follow-up	8	9	5	5
Overall Study Physician Decision	0	2	2	2
Overall Study Protocol Violation	2	0	0	0
Overall Study Withdrawal by Subject	8	17	7	22
Overall Study Personal Reason	2	3	1	3

Baseline Characteristics

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Hemoglobin A1c Analysis Population Description: All randomized participants who had a HbA1c baseline value.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	5 mg Tirzepatide n=359 Participants 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.	10 mg Tirzepatide n=361 Participants 10 mg tirzepatide administered SC once a week.	15 mg Tirzepatide n=359 Participants 15 mg tirzepatide administered SC once a week SC.	Insulin Degludec n=365 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.	Total n=1444 Participants Total of all reporting groups
Age, Continuous	57.20 years STANDARD_DEVIATION 10.13 • n=359 Participants	57.40 years STANDARD_DEVIATION 9.66 • n=361 Participants	57.50 years STANDARD_DEVIATION 10.24 • n=359 Participants	57.50 years STANDARD_DEVIATION 10.08 • n=365 Participants	57.40 years STANDARD_DEVIATION 10.02 • n=1444 Participants
Sex: Female, Male Female	158 Participants n=359 Participants	165 Participants n=361 Participants	165 Participants n=359 Participants	148 Participants n=365 Participants	636 Participants n=1444 Participants
Sex: Female, Male Male	201 Participants n=359 Participants	196 Participants n=361 Participants	194 Participants n=359 Participants	217 Participants n=365 Participants	808 Participants n=1444 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	109 Participants n=359 Participants	108 Participants n=361 Participants	96 Participants n=359 Participants	108 Participants n=365 Participants	421 Participants n=1444 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	247 Participants n=359 Participants	253 Participants n=361 Participants	259 Participants n=359 Participants	256 Participants n=365 Participants	1015 Participants n=1444 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=359 Participants	0 Participants n=361 Participants	4 Participants n=359 Participants	1 Participants n=365 Participants	8 Participants n=1444 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=359 Participants	1 Participants n=361 Participants	1 Participants n=359 Participants	2 Participants n=365 Participants	4 Participants n=1444 Participants
Race (NIH/OMB) Asian	20 Participants n=359 Participants	19 Participants n=361 Participants	20 Participants n=359 Participants	19 Participants n=365 Participants	78 Participants n=1444 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=359 Participants	0 Participants n=361 Participants	2 Participants n=359 Participants	1 Participants n=365 Participants	4 Participants n=1444 Participants
Race (NIH/OMB) Black or African American	13 Participants n=359 Participants	12 Participants n=361 Participants	8 Participants n=359 Participants	11 Participants n=365 Participants	44 Participants n=1444 Participants
Race (NIH/OMB) White	324 Participants n=359 Participants	329 Participants n=361 Participants	327 Participants n=359 Participants	332 Participants n=365 Participants	1312 Participants n=1444 Participants
Race (NIH/OMB) More than one race	1 Participants n=359 Participants	0 Participants n=361 Participants	1 Participants n=359 Participants	0 Participants n=365 Participants	2 Participants n=1444 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=359 Participants	0 Participants n=361 Participants	0 Participants n=359 Participants	0 Participants n=365 Participants	0 Participants n=1444 Participants
Region of Enrollment Argentina	57 Participants n=359 Participants	54 Participants n=361 Participants	56 Participants n=359 Participants	57 Participants n=365 Participants	224 Participants n=1444 Participants
Region of Enrollment Austria	7 Participants n=359 Participants	8 Participants n=361 Participants	4 Participants n=359 Participants	8 Participants n=365 Participants	27 Participants n=1444 Participants
Region of Enrollment Greece	33 Participants n=359 Participants	35 Participants n=361 Participants	35 Participants n=359 Participants	34 Participants n=365 Participants	137 Participants n=1444 Participants
Region of Enrollment Hungary	36 Participants n=359 Participants	37 Participants n=361 Participants	37 Participants n=359 Participants	37 Participants n=365 Participants	147 Participants n=1444 Participants
Region of Enrollment Italy	6 Participants n=359 Participants	8 Participants n=361 Participants	8 Participants n=359 Participants	8 Participants n=365 Participants	30 Participants n=1444 Participants
Region of Enrollment Poland	33 Participants n=359 Participants	33 Participants n=361 Participants	33 Participants n=359 Participants	33 Participants n=365 Participants	132 Participants n=1444 Participants
Region of Enrollment Puerto Rico	8 Participants n=359 Participants	7 Participants n=361 Participants	11 Participants n=359 Participants	9 Participants n=365 Participants	35 Participants n=1444 Participants
Region of Enrollment Romania	54 Participants n=359 Participants	54 Participants n=361 Participants	53 Participants n=359 Participants	53 Participants n=365 Participants	214 Participants n=1444 Participants
Region of Enrollment South Korea	9 Participants n=359 Participants	10 Participants n=361 Participants	8 Participants n=359 Participants	9 Participants n=365 Participants	36 Participants n=1444 Participants
Region of Enrollment Spain	21 Participants n=359 Participants	21 Participants n=361 Participants	22 Participants n=359 Participants	22 Participants n=365 Participants	86 Participants n=1444 Participants
Region of Enrollment Taiwan	9 Participants n=359 Participants	8 Participants n=361 Participants	10 Participants n=359 Participants	9 Participants n=365 Participants	36 Participants n=1444 Participants
Region of Enrollment Ukraine	11 Participants n=359 Participants	11 Participants n=361 Participants	12 Participants n=359 Participants	11 Participants n=365 Participants	45 Participants n=1444 Participants
Region of Enrollment United States	75 Participants n=359 Participants	75 Participants n=361 Participants	70 Participants n=359 Participants	75 Participants n=365 Participants	295 Participants n=1444 Participants
Hemoglobin A1c	8.17 Percentage of HbA1c STANDARD_DEVIATION 0.89 • n=358 Participants • HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Hemoglobin A1c Analysis Population Description: All randomized participants who had a HbA1c baseline value.	8.18 Percentage of HbA1c STANDARD_DEVIATION 0.89 • n=360 Participants • HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Hemoglobin A1c Analysis Population Description: All randomized participants who had a HbA1c baseline value.	8.21 Percentage of HbA1c STANDARD_DEVIATION 0.94 • n=359 Participants • HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Hemoglobin A1c Analysis Population Description: All randomized participants who had a HbA1c baseline value.	8.12 Percentage of HbA1c STANDARD_DEVIATION 0.94 • n=360 Participants • HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Hemoglobin A1c Analysis Population Description: All randomized participants who had a HbA1c baseline value.	8.17 Percentage of HbA1c STANDARD_DEVIATION 0.91 • n=1437 Participants • HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Hemoglobin A1c Analysis Population Description: All randomized participants who had a HbA1c baseline value.

PRIMARY outcome

Timeframe: Baseline, Week 52

Population: All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date +7 days)

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=291 Participants 10 mg tirzepatide administered SC once a week.	15 mg Tirzepatide n=294 Participants 15 mg tirzepatide administered SC once a week SC.	Insulin Degludec n=317 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.	Insulin Degludec Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.
Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)	-2.20 Percentage of HbA1c Standard Error 0.051	-2.37 Percentage of HbA1c Standard Error 0.050	-1.34 Percentage of HbA1c Standard Error 0.049	—

SECONDARY outcome

Timeframe: Baseline, Week 52

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=312 Participants 10 mg tirzepatide administered SC once a week.	15 mg Tirzepatide n=317 Participants 15 mg tirzepatide administered SC once a week SC.	Insulin Degludec Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.	Insulin Degludec Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.
Change From Baseline in HbA1c (5 mg)	-1.93 Percentage of HbA1c Standard Error 0.050	-1.34 Percentage of HbA1c Standard Error 0.049	—	—

SECONDARY outcome

Timeframe: Baseline, Week 52

LS mean was determined by MMRM model with Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as covariates.

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=310 Participants 10 mg tirzepatide administered SC once a week.	15 mg Tirzepatide n=291 Participants 15 mg tirzepatide administered SC once a week SC.	Insulin Degludec n=295 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.	Insulin Degludec n=317 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.
Change From Baseline in Body Weight	-7.5 Kilograms (kg) Standard Error 0.37	-10.7 Kilograms (kg) Standard Error 0.37	-12.9 Kilograms (kg) Standard Error 0.37	2.3 Kilograms (kg) Standard Error 0.37

SECONDARY outcome

Timeframe: Baseline, Week 52

LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=309 Participants 10 mg tirzepatide administered SC once a week.	15 mg Tirzepatide n=291 Participants 15 mg tirzepatide administered SC once a week SC.	Insulin Degludec n=293 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.	Insulin Degludec n=314 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.
Change From Baseline in Fasting Serum Glucose	-48.2 milligram per Deciliter (mg/dL) Standard Error 1.82	-54.8 milligram per Deciliter (mg/dL) Standard Error 1.86	-59.2 milligram per Deciliter (mg/dL) Standard Error 1.85	-55.7 milligram per Deciliter (mg/dL) Standard Error 1.81

SECONDARY outcome

Timeframe: Week 52

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing. Missing endpoint measures are imputed by predictions from an MMRM analysis model using observed data in the efficacy analysis set and adjusted for Baseline Value, Pooled Country, Baseline OAM Use (Met, Met plus SGLT-2i), Treatment, Visit and Visit\*Treatment.

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=353 Participants 10 mg tirzepatide administered SC once a week.	15 mg Tirzepatide n=350 Participants 15 mg tirzepatide administered SC once a week SC.	Insulin Degludec n=353 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.	Insulin Degludec n=351 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.
Percentage of Participants Achieving an HbA1c Target Value of <7%	82.44 percentage of participants	89.71 percentage of participants	92.63 percentage of participants	61.25 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 52

The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. LS mean was determined by mixed-model repeated measures (MMRM) model with variables Baseline + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=281 Participants 10 mg tirzepatide administered SC once a week.	15 mg Tirzepatide n=263 Participants 15 mg tirzepatide administered SC once a week SC.	Insulin Degludec n=274 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.	Insulin Degludec n=288 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values	-52.6 mg/dL Standard Error 1.20	-59.7 mg/dL Standard Error 1.22	-60.6 mg/dL Standard Error 1.20	-48.0 mg/dL Standard Error 1.18

SECONDARY outcome

Timeframe: Week 52

Percentage of Participants who Achieved Weight Loss ≥5%

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=353 Participants 10 mg tirzepatide administered SC once a week.	15 mg Tirzepatide n=350 Participants 15 mg tirzepatide administered SC once a week SC.	Insulin Degludec n=353 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.	Insulin Degludec n=351 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.
Percentage of Participants Who Achieved Weight Loss ≥5%	66.01 percentage of participants	83.71 percentage of participants	87.82 percentage of participants	6.27 percentage of participants

SECONDARY outcome

Timeframe: Week 52

DTSQc, an 8-item questionnaire, assesses relative change in treatment satisfaction perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia from baseline to week 52 or early termination.The treatment satisfaction score ranges from -18 to 18 where the higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. The hyperglycemia and hypoglycemia scores range from -3 to 3 where negative scores indicate fewer problems with blood glucose levels and positive scores indicate more problems than before. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline DTSQs + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment (Type III sum of squares).

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=306 Participants 10 mg tirzepatide administered SC once a week.	15 mg Tirzepatide n=293 Participants 15 mg tirzepatide administered SC once a week SC.	Insulin Degludec n=292 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.	Insulin Degludec n=313 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score Hyperglycemia	-1.4 units on a scale Standard Error 0.11	-1.4 units on a scale Standard Error 0.11	-1.6 units on a scale Standard Error 0.11	-1.1 units on a scale Standard Error 0.11
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score Hypoglycemia	-1.1 units on a scale Standard Error 0.12	-0.9 units on a scale Standard Error 0.12	-1.0 units on a scale Standard Error 0.12	-0.7 units on a scale Standard Error 0.12
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score Treatment Satisfaction Score	15.6 units on a scale Standard Error 0.27	15.5 units on a scale Standard Error 0.28	15.6 units on a scale Standard Error 0.28	12.6 units on a scale Standard Error 0.27

SECONDARY outcome

Timeframe: Baseline through Safety Follow-Up (Up to Week 56)

The hypoglycemia events were defined by participant reported events with blood glucose \<54mg/dL (\<3.0 mmol/L) or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: Number of episodes = Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment, with log (exposure in days/365.25) as an offset variable.

Outcome measures

Outcome measures
Measure	10 mg Tirzepatide n=356 Participants 10 mg tirzepatide administered SC once a week.	15 mg Tirzepatide n=360 Participants 15 mg tirzepatide administered SC once a week SC.	Insulin Degludec n=359 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.	Insulin Degludec n=358 Participants Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia	0.0137 Episodes/participant/365.25 days Standard Error 0.0056	0.0108 Episodes/participant/365.25 days Standard Error 0.0044	0.0275 Episodes/participant/365.25 days Standard Error 0.0143	0.1020 Episodes/participant/365.25 days Standard Error 0.0568

Adverse Events

5 mg Tirzepatide

Serious events: 29 serious events

Other events: 124 other events

Deaths: 1 deaths

10 mg Tirzepatide

Serious events: 20 serious events

Other events: 157 other events

Deaths: 2 deaths

15 mg Tirzepatide

Serious events: 26 serious events

Other events: 179 other events

Deaths: 1 deaths

Insulin Degludec

Serious events: 22 serious events

Other events: 66 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	5 mg Tirzepatide n=358 participants at risk 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.	10 mg Tirzepatide n=360 participants at risk 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.	15 mg Tirzepatide n=359 participants at risk 15 mg tirzepatide administered SC once a week SC.	Insulin Degludec n=360 participants at risk Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values.
Gastrointestinal disorders Abdominal pain	2.0% 7/358 • Number of events 7 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.7% 17/360 • Number of events 28 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.4% 23/359 • Number of events 46 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 4/360 • Number of events 5 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Diarrhoea	15.4% 55/358 • Number of events 92 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	16.4% 59/360 • Number of events 97 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	15.6% 56/359 • Number of events 107 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	3.9% 14/360 • Number of events 18 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Dyspepsia	3.9% 14/358 • Number of events 14 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.9% 32/360 • Number of events 39 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.0% 18/359 • Number of events 28 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/360 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Nausea	11.5% 41/358 • Number of events 86 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	22.5% 81/360 • Number of events 140 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	23.7% 85/359 • Number of events 240 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.7% 6/360 • Number of events 6 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Vomiting	5.9% 21/358 • Number of events 29 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	9.4% 34/360 • Number of events 53 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	10.0% 36/359 • Number of events 63 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 4/360 • Number of events 4 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Nasopharyngitis	3.1% 11/358 • Number of events 11 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	3.9% 14/360 • Number of events 15 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 15/359 • Number of events 16 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.1% 22/360 • Number of events 27 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Lipase increased	5.9% 21/358 • Number of events 25 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.4% 16/360 • Number of events 18 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.6% 20/359 • Number of events 21 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.9% 7/360 • Number of events 7 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Decreased appetite	6.1% 22/358 • Number of events 23 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	10.3% 37/360 • Number of events 59 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	12.0% 43/359 • Number of events 54 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.56% 2/360 • Number of events 2 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Vascular disorders Hypertension	3.1% 11/358 • Number of events 11 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.9% 7/360 • Number of events 8 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	3.1% 11/359 • Number of events 11 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.8% 21/360 • Number of events 22 • Baseline Up To 56 Weeks All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60